Extracellular Vesicles: Unique Intercellular Delivery Vehicles

AbstractExtracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs.

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Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽

10.3390/pharmaceutics13040492 ◽

2021 ◽

Vol 13 (4) ◽

pp. 492

Author(s):

Charlotte A. René ◽

Robin J. Parks

Keyword(s):

Central Nervous System ◽

Endothelial Cells ◽

Nervous System ◽

Blood Brain Barrier ◽

Extracellular Vesicles ◽

Therapeutic Agents ◽

Target Cells ◽

Significant Barrier ◽

The Central Nervous System ◽

Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

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Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing

Journal of Extracellular Vesicles ◽

10.1002/jev2.12076 ◽

2021 ◽

Vol 10 (5) ◽

Author(s):

Xingang Yao ◽

Pin Lyu ◽

Kyung Yoo ◽

Manish Kumar Yadav ◽

Ravi Singh ◽

...

Keyword(s):

Genome Editing ◽

Extracellular Vesicles ◽

Delivery Vehicles

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Cancer therapy based on extracellular vesicles as drug delivery vehicles

Journal of Controlled Release ◽

10.1016/j.jconrel.2020.08.018 ◽

2020 ◽

Vol 327 ◽

pp. 296-315 ◽

Cited By ~ 2

Author(s):

Laura Cabeza ◽

Gloria Perazzoli ◽

Mercedes Peña ◽

Ana Cepero ◽

Cristina Luque ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Therapy ◽

Extracellular Vesicles ◽

Drug Delivery Vehicles ◽

Delivery Vehicles

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Extracellular vesicles: Natural liver‐accumulating drug delivery vehicles for the treatment of liver diseases

Journal of Extracellular Vesicles ◽

10.1002/jev2.12030 ◽

2020 ◽

Vol 10 (2) ◽

Author(s):

Gensheng Zhang ◽

Xiaofang Huang ◽

Huiqing Xiu ◽

Yan Sun ◽

Jiming Chen ◽

...

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Liver Diseases ◽

Drug Delivery Vehicles ◽

Delivery Vehicles

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Extracellular Vesicles for Cancer Therapy: Impact of Host Immune Response

Cells ◽

10.3390/cells9010224 ◽

2020 ◽

Vol 9 (1) ◽

pp. 224 ◽

Cited By ~ 3

Author(s):

Katie E. Gilligan ◽

Róisín M. Dwyer

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Cancer Therapeutics ◽

Cell Of Origin ◽

Major Focus ◽

Negative Effects ◽

Isolation And Characterization ◽

Cancer Setting ◽

Delivery Vehicles ◽

Potential Therapeutics

In recent times, extracellular vesicles (EVs) have come under the spotlight as potential therapeutics for cancer, due to the relative ease of manipulation of contents and potential for tumor targeting. The use of EVs as delivery vehicles may bypass some of the negative effects associated with cell-based carriers, and there has been a major focus on defining EV subtypes, establishing transparent nomenclature, and isolation and characterization techniques. EVs are believed to be a fingerprint of the secreting cell and so researchers harness the positive aspects of a particular cell of origin, and can then further modify EV contents to improve therapeutic efficacy. In this review, we highlight studies employing EVs as cancer therapeutics that have reported on immune response. As we rapidly advance towards potential application in the clinical setting, the question of immune response to EV administration in the cancer setting has become critically important.

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Advances in therapeutic applications of extracellular vesicles

Science Translational Medicine ◽

10.1126/scitranslmed.aav8521 ◽

2019 ◽

Vol 11 (492) ◽

pp. eaav8521 ◽

Cited By ~ 118

Author(s):

Oscar P. B. Wiklander ◽

Meadhbh Á. Brennan ◽

Jan Lötvall ◽

Xandra O. Breakefield ◽

Samir EL Andaloussi

Keyword(s):

Stem Cell ◽

Extracellular Vesicles ◽

Tissue Regeneration ◽

Immune Modulation ◽

Lipid Membrane ◽

Therapeutic Agents ◽

Bioactive Components ◽

Pathological Conditions ◽

Delivery Vehicles ◽

And Function

Extracellular vesicles (EVs) are nanometer-sized, lipid membrane–enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents. EVs can potentiate tissue regeneration, participate in immune modulation, and function as potential alternatives to stem cell therapy, and bioengineered EVs can act as delivery vehicles for therapeutic agents. Here, we cover recent approaches and advances of EV-based therapies.

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Multifunctional Applications of Engineered Extracellular Vesicles in the Treatment of Cancer

Endocrinology ◽

10.1210/endocr/bqaa250 ◽

2021 ◽

Vol 162 (3) ◽

Author(s):

Fernanda G Kugeratski ◽

Kathleen M McAndrews ◽

Raghu Kalluri

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Anticancer Agents ◽

Antitumor Immunity ◽

Therapeutic Delivery ◽

Signaling Mechanisms ◽

Delivery Vehicles ◽

Complex Signaling ◽

Interfering Rna ◽

Target Cancer

Abstract Extracellular vesicles (EVs) are key players of intercellular communication in the physiological and pathological setting. In cancer, EVs mediate complex signaling mechanisms between cancer cells and the tumor microenvironment (TME), and can influence tumor progression and the response to existing therapies. Importantly, EVs can be loaded with therapeutic agents and modified to display tumor-targeting molecules. In the field of nanomedicine, EVs have been engineered to serve as therapeutic delivery vehicles for several anticancer agents, including antibodies, chemotherapy, compounds, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats–associated endonuclease 9), and small interfering RNA (siRNA). Notably, the engineered EVs were shown to suppress malignant features of cancer cells, to elicit antitumor immunity, and to decrease tumor angiogenesis. Here, we review the EV-based therapies designed to target cancer cells and to educate components of the TME to drive antitumor responses. These studies illustrate the multifunctional applications of EVs in the development of anticancer therapies and their translational potential for cancer treatment.

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Extracellular Vesicles as Therapeutics for Brain Injury and Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666191014164950 ◽

2019 ◽

Vol 25 (33) ◽

pp. 3500-3505 ◽

Cited By ~ 8

Author(s):

Dinesh Upadhya ◽

Ashok K. Shetty

Keyword(s):

Stem Cells ◽

Brain Injury ◽

Extracellular Vesicles ◽

Lipid Membranes ◽

Brain Dysfunction ◽

Cns Injury ◽

Drug Delivery Vehicles ◽

Beneficial Effects ◽

Tremendous Importance ◽

Delivery Vehicles

: Extracellular vesicles (EVs) are gaining tremendous importance in comprehending central nervous system (CNS) function and treating neurological disorders because of their role in intercellular communication and reparative processes, and suitability as drug delivery vehicles. Since EVs have lipid membranes, they cross the blood-brain barrier easily and communicate with target neurons and glia even deep inside the brain. EVs from various sources have been isolated, characterized, and tailored for promoting beneficial effects in conditions, such as brain injury and disease. Particularly, EVs isolated from mesenchymal stem cells and neural stem cells have shown promise for alleviating brain dysfunction after injury or disease. Such properties of stem cell-derived EVs have great importance for clinical applications, as EV therapy can avoid several concerns typically associated with cell therapy. This minireview confers the competence of EVs for improving brain function by modulating CNS injury and disease.

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